Summary

Migraine headache is responsible for significantly more healthcare resource and lost labour costs than previously reported. Costs associated with migraine were assessed via a survey conducted in 940 patients, 70% of whom responded. All met the International Headache Society’s diagnostic criteria for migraine and had participated in one of two multicentre, single-dose, parallel-group, randomised, placebo-controlled clinical trials designed to assess the efficacy of an anti-migraine compound. Migraine frequency and costs, in terms of healthcare resource utilisation and lost labour (decreased productivity and missed workdays), were assessed. Over 90% of respondents visited a clinic and nearly 50% presented to an emergency room for treatment of migraine-related symptoms at least once in the year prior to the survey. These 648 respondents used an estimated $US529 199 per year in healthcare services. 89% of employed respondents reported that job performance was adversely affected by migraine and over 50% of them missed at least two days of work per month. Depending on the estimates used for migraine prevalence and using 1986 estimates of median earnings for the US work force, the extrapolated costs to employers ranged from $US5.6 billion to $US17.2 billion dollars annually due to decreased productivity and missed work days. The cost of migraine is not fully appreciated by the medical community or by society.

Summary

Aspirin (acetylsalicylic acid) and its salicylate derivatives are effective antipyretic, analgesic, and anti-inflammatory agents that are still very widely used by the elderly despite the advent of newer, potentially safer nonsteroidal anti-inflammatory drugs (NSAIDs). However, none of the new NSAIDs have been proven to be more effective than aspirin or salicylic acid. Chronic salicylate intoxication which is most common in the elderly, may occur with therapeutic doses. Increased toxicity in older patients often appears due to inadvertent overdosage. Dual prescribing or additional use of nonprescription salicylates are some causes of unwitting long term toxicity.

According to some studies, systemic clearance of salicylate (mainly by hepatic metabolism) is reduced with age, as is renal elimination. These changes are of increased importance in the elderly using high therapeutic doses of salicylates when metabolism is saturated and more unchanged drug is available for renal excretion. In the face of renal impairment, the risk of toxicity is increased.

The diagnosis of acute salicylate intoxication generally does not pose diagnostic problems. Patients often present with a history of intentional overdose, with hyperventilation, fever, and nausea. The diagnosis can be confirmed by measuring serum salicylate concentrations. Chronic intoxication often poses a diagnostic dilemma with atypical presentations mimicking other disease states such as diabetic ketoacidosis, delirium, cerebrovascular accident, myocardial infarction or cardiac failure. The diagnosis of salicylate intoxication should be borne in mind when an older patient presents with recent deterioration in acitivities of daily living with no known cause. Plasma salicylate concentrations should be measured if salicylate intoxication is suspected, even if there is no documented history of salicylate ingestion. The risk of salicylate nephrotoxicity is also increased with age, and upper gastrointestinal haemorrhage is associated with increased mortality in older age groups.

Treatment of acute toxicity consists of prompt recognition of salicylate intoxication, use of activated charcoal, correction of acid-base abnormalities, general supportive measures, and if concentrations are extremely high, dialysis can be effectively used. Chronic toxicity, which can occur even with marginally high salicylate concentrations, is treated with drug withdrawal and supportive therapy.

Chronic salicylate toxicity can be averted by prescription of conservative doses of drug, avoidance of concomitant use of different salicylate preparations, and therapeutic monitoring to guide dosage. Renal function should be monitored to detect nephrotoxicity from chronic salicylate therapy. Patients should be regularly screened for evidence of gastrointestinal bleeding. Use of aspirin and other NSAIDs should be avoided, if possible, in older patients with a history of upper gastrointestinal haemorrhage. If aspirin therapy is required, misoprostol prophylaxis can be employed.

Summary

Two new cases of alexia without agraphia are presented. Pertinent clinical findings, anatomy, pathophysiology and differential diagnoses are reviewed. The importance of carefully examining the inferior portion of the left side of the splenium of the corpus callosum on CT and/or MR scans in patients who present with this clinical syndrome is stressed.

A model is proposed to explain the etiology of pathological handedness. Developmental instability, caused by elevated genotypic homozygosity, environmental disturbances, or their interaction, overrides programmed laterality and handedness in the same way that it perturbs the bilaterally symmetrical expression of morphological and metric traits. The model predicts that pathological handedness should be elevated among individuals with higher than average homozygosity and individuals who have developed under unfavorable uterine environments. Suggestions are offered for specific populations in which the predictions may be tested.

Child abuse is a complex problem involving society, the community, and the family. In our social system, children historically have been viewed as the property of their parents, who have the right to punish their children as they see fit (Kempe, Silverman, Steele, Droegemueller, & Silver, 1962). This perspective changed in 1962, when Kempe coined the term “the battered child syndrome” (Kempe & Helfer, 1972). From 1963 to 1968, all states passed laws which required reporting, investigating, and protecting children who were abused (Radbill, 1968). In 1974, the National Child Abuse Prevention and Treatment Act was passed. However, it is only in the past few years that the seriousness and scope of the problem have been fully realized. Indeed, data from more recent nationwide surveys have underscored the magnitude of the problem. For example, there are indications that between 10 and 16 children out of every 1,000 in the United States are abused and/or neglected annually (National Center on Child Abuse and Neglect, 1988). And reports of incidents have risen dramatically across most states.

This chapter presents an overview of behavioral sexual differentiation in humans and presents data from our laboratory and other laboratories that highlight the importance of early (prenatal and/or postnatal) hormonal stimulation by androgenic substances in this process. Data derived from the study of individuals who were exposed to atypical levels of endogenous hormones or to exogenous compounds with an androgenic potential are presented to provide insight into the normal process underlying the emergence of sex differences (see also Reinisch, Ziemba-Davis, & Sanders, 1991).

To accurately assess the nature and extent of brain injury, is it important to know the patient’s handedness? Evidence from both clinical and normal populations indicates that the organization of brain functions differs for right- and left-handers. In general, left-handers are less lateralized for linguistic, visuospatial, and other cognitive and affective processes, and are likely to show bilateral representation of cognitive functions. Lack of standardization in the measurement of handedness and the influence of other variables such as familial sinistrality, sex, and reasoning ability on brain organization make it difficult to specify for any particular individual. However, awareness of the identified modifiers of brain organization and knowledge of findings on handedness relating to lateralized functions can assist the neuropsychologist in making more accurate diagnoses and inferences. This chapter will present current research findings on laterality and handedness and apply them to issues of clinical concern.

Nature (1992-11-12) 360: 161-163
, November 12, 1992

NEUROPSYCHIATRIC disorders such as anxiety, depression, migraine, vasospasm and epilepsy may involve different subtypes of the 5-hydroxytryptamine (5-HT) receptor1,2. The IB subtype, which has a unique pharmacology, was first identified in rodent brain3–7. But a similar receptor could not be detected in human brain6, suggesting the absence in man of a receptor with equivalent function. Recently a human receptor gene was isolated (designated 5-HT1B receptor8,9, 5-HT1Dβ receptor10,11, or S12 receptor12) which shares 93% identity of the deduced protein sequence with rodent 5-HT1B receptors13–15. Although this receptor is identical to rodent 5-HT1B receptors in binding to 5-HT, it differs profoundly in binding to many drugs. Here we show that replacement of a single amino acid in the human receptor (threonine at residue 355) with a corresponding asparagine found in rodent 5-HT1B receptors renders the pharmacology of the receptors essentially identical. This demonstrates that the human gene does indeed encode a 1B receptor, which is likely to have the same biological functions as the rodent 5-HT1B receptor. In addition, these findings show that minute sequence differences between homologues of the same receptor from different species can cause large pharmacological variation. Thus, drug–receptor interactions should not be extrapolated from animal to human species without verification.

The diagnosis of epilepsy is often a rather straightforward matter. The clinical episodes are classic, the EEG is confirmatory, and the response to medications is positive. At other times the picture is murky. The spells are of an uncharacteristic type, EEG findings of uncertain clinical significance are obtained, and the neurologist subsequently struggles with issues of differential diagnosis, for example, are the spells caused by cardiac disease, cerebrovascular disease, migraine, or some other neurological or systemic process? Often, but not always, the etiology underlying these nonepileptic phenomena is identified and treated, and the patient subsequently improves. In both of these scenarios, the neurologist does not question the organic nature of the attacks, and consultation from the psychology service is neither mandatory nor asked for.